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1、FEBS18714FEBSLetters412(1997)21-29Inheritedretinaldegeneration:basicFGFinducesphagocyticcompetenceinculturedRPEcellsfromRCSratsM.J.McLaren1>a'*,G.Inanab'^DepartmentofPhysiologyandBiophysics,UniversityofMiamiSchoolofMedicine,Miami,FL33136,USAhLaboratoryofMolecularGenetics,BascomPalmerEyeInstitute,
2、UniversityofMiamiSchoolofMedicine,Miami,FL33136,USAReceived17March1997;revisedversionreceived28April1997scavengerreceptorCD36[14],aswellasotherunknownpro-AbstractInRCSrats,theretinalpigmentepithelium(RPE)isteinsofRPEplasmamembranes[15,16],havebeenproposeddefectiveinphagocytosisofphotoreceptormemb
3、ranes.WehavepreviouslyshownreducedexpressionofbasicfibroblastgrowthascandidatesfortheROSreceptor.factor(bFGF)intheRPEof7-10-day-oldRCSrats.ThisstudyBasicFGF(FGF-2)isawidelydistributedheparin-bindingusingprimaryRPEculturesfromratsofthisagedemonstratesgrowthfactorwitharemarkablydiverserangeofaction
4、scrit-thatthephagocyticdefectinthemutantRPEcanbeovercomeicalinnormaldevelopment,reproduction,angiogenesisandbytreatmentwithbFGF,byamechanisminvolvinggeneresponsesofthenervoussystemtoinjury[17-23].AlthoughtranscriptionandthatnormalRPEphagocytosis,alsorequiringintraocularinjectionofseveraldifferent
5、neurotrophicfactorstranscription,isblockedbyabFGFneutralizingantibody.TheincludingbFGFhasbeenshowntoprotectnormalratphoto-combineddatapointtoaroleforbFGFinthenormalmechanismreceptorsfrominsultssuchaslightdamage[24]andphysicalofRPEphagocytosisandtheRCSdefect.trauma[25],onlybFGFhasbeenshowntodelayt
6、hedemise©1997FederationofEuropeanBiochemicalSocieties.ofthephotoreceptorsintheRCSmodelofinheritedretinaldegeneration[26].WehaverecentlyshownthatbFGFmRNAKeywords:Basicfibroblastgrowthfactor;RPEcell;andproteinexpressionaremarkedlydown-regulatedinthePhagocytosis;RCSrat;InheritedretinaldegenerationRP
7、EofRCSratsduringthedevelopmentalperiod(P7-P12)whenexpressionofthephagocyticdefectfirstoccursinvivo[27].SincetheprimarygeneticdefectresidesintheRPEin1.Introductionthismodel[7],thepresentinvestigationtestedwhetherexoge-n